Methods of treating deep and early-stage pressure induced tissue damage

ABSTRACT

The present disclosure provides methods for evaluating tissue damage and the use of spatial variation in Sub-Epidermal Moisture (SEM) values to determine damaged tissue for clinical intervention. The present disclosure provides methods of identifying deep and early-stage pressure-induced injuries or ulcers (PI/PU). The present disclosure provides algorithm for computing SEM delta values which inform clinical decision-making for developing intact skin PI/PUs including suspected deep tissue injury (sDTI) and Stage I PI/PUs.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of priority of U.S. ProvisionalApplication 63/145,349 filed Feb. 3, 2021, and U.S. ProvisionalApplication 63/304,066 filed Jan. 28, 2022, each of which is hereinincorporated by reference in its entirety.

BACKGROUND OF THE INVENTION Field of the Invention

The present disclosure provides a method for evaluating the use ofspatial variation in Sub-Epidermal Moisture (SEM) values to determinedamaged tissue for clinical intervention.

Description of Related Art

Pressure injuries or ulcers (PI/PUs) remain a frequently reportedpreventable patient harm in many countries. Despite improving carepathways in PI/PU prevention, PI/PUs are the only hospital-acquiredcondition whose incidence has worsened since 2014. Annually, PI/PUsoccur in more than 2.5 million US patients, and are linked toapproximately 60,000 deaths. Management of PI/PUs is cost intensive:overall annual costs in the US are estimated to exceed $26.8 billion,with per-patient costs ranging from $500 to $70,000. In the UK, treatingPI/PUs costs the NHS £0.5-2.1 billion annually, accounting forapproximately 4% of total expenditure. The advent of COVID-19 hasincreased the number of patients requiring intensive care and theincreased lengths of stay associated with COVID-19 treatment intensifythe risk factors associated with PI/ICUs and are likely to increaseglobal incidence rates of PI/PUs.

Current standard of care (SoC) relies heavily on validated riskassessment tool scores (RATS) (e.g., Braden and Waterlow 1) to evaluatea patient's risk of developing PI/PUs. RATs are supplemented by a skinand tissue assessment (STA), using visual and palpation tests.Healthcare practitioners (HCPs) are guided to assess for changes in skincolor, blanchability, temperature, hardness and other visible orpalpable indicators of injury. Stage I PI/PUs are described as an areaof ‘persistent focal edema’ in the International Classification forDisease (ICD-10 code L89).

Subjective clinical judgment of HCPs, informed by RATS and STAs have asensitivity of 50.6% and specificity of 60.1%—in other words approachingrandomness. Additionally, there is a diagnostic latency—a gap betweenthe onset of microscopic damage and the time at which it is detected andconfirmed at the skin surface under the current SoC. Early microscopictissue damage and the associated inflammatory response results influctuations in localized tissue oedema, termed sub-epidermal moisture(SEM), a systemic response that unfolds even before visual epidermalskin damage. Current RATs and clinical judgement are ineffective inachieving timely detection of non-visible sub-epidermal injuries. Thisineffectiveness is further exacerbated in darkly pigmented skin. Relyingsolely on current RATs and STAs, early detection of developing PI/PUsand timely, appropriate, anatomy-specific interventions is impossiblewithout an objective diagnostic test.

SUMMARY OF THE INVENTION

In an aspect, the present disclosure provides for, and includes, methodsfor assessing tissue health at and around a target region, comprisingthe steps of: obtaining a first plurality of SEM measurements at a firstplurality of locations within a first tissue assessment area, obtaininga second plurality of SEM measurements at a second plurality oflocations within a second tissue assessment area, calculating a firstaverage of the first plurality of SEM measurements, calculating a secondaverage of the second plurality of SEM measurements, calculating adifference between the second average and the first average, flaggingthat the tissue is damaged if the difference is greater than or equal toa cut-off threshold.

In an aspect, a cut-off threshold is a predetermined number. In anaspect, a cut-off threshold is a number ranging from about 0.6 to about0.9. In an aspect, a cut-off threshold is about 0.6. In an aspect, acut-off threshold is about 0.7. In an aspect, a cut-off threshold isabout 0.8. In an aspect, a cut-off threshold is about 0.9.

In an aspect, a first tissue assessment area is a circle centered on atarget region and having a first radial distance. In an aspect, a secondtissue assessment area is an annulus centered on a target region andhaving a second inner radial distance and a third outer radial distancefrom the target region. In an aspect, a second inner radial distance isgreater than or equal to a first radial distance. In an aspect, a thirdouter radial distance is greater than a second inner radial distance.

In an aspect, a first plurality of locations comprises a location in thecenter of a circle. In an aspect, a first plurality of locationscomprises spatially distinct points within a circle. In an aspect, afirst plurality of locations comprises spatially distinct points alongone or more concentric rings within a circle, and wherein the one ormore concentric rings are centered on a target region. In an aspect, afirst plurality of locations comprises spatially distinct points alongtwo lines dividing a circle into four quadrants. In an aspect, a secondplurality of locations comprises spatially distinct points within anannulus. In an aspect, a second plurality of locations comprisesspatially distinct points along one or more concentric rings within anannulus, and wherein the one or more concentric rings are centered on atarget region. In an aspect, a second plurality of locations comprisesspatially distinct points along two lines dividing an annulus into fourquadrants.

In an aspect, a first plurality of SEM measurements consists of 1 to 9measurements. In an aspect, a second plurality of SEM measurementsconsists of 3 to 8 measurements. In an aspect, a target region is a bonyprominence selected from the group consisting of a sacrum, a heel, asternum, a scapula, an elbow, a thoracic spine, a trochanter, anischium, and an ear. In an aspect, a target region is a flesh tissue. Inan aspect, a target region is within an erythema. In an aspect, a targetregion is within a healthy tissue.

BRIEF DESCRIPTION OF THE FIGURES

Some aspects of the disclosure are herein described, by way of exampleonly, with reference to the accompanying drawings. With specificreference now to the drawings in detail, it is stressed that theparticulars shown are by way of example and are for purposes ofillustrative discussion of aspects of the disclosure. In this regard,the description and the drawings, considered alone and together, makeapparent to those skilled in the art how aspects of the disclosure maybe practiced.

FIG. 1A—Sample SEM measurement locations according to protocol 003 inthe prior art.

FIG. 1B—Sample SEM measurement locations according to protocol 004 inthe prior art.

FIG. 2A—Sample SEM measurement locations in accordance with the methodsin the present disclosure.

FIG. 2B—Sample SEM measurement results obtained in accordance with themethods in the present disclosure, represented as an SEM map.

FIG. 3—Receiver operating characteristics (ROC) curve illustratingdiagnostic sensitivity and specificity in detecting pressureulcer/injury relative to skin and tissue assessment using the methods inthe present disclosure.

DETAILED DESCRIPTION

The present disclosure describes measurement of SEM values at and aroundhealthy and damaged tissues, and the method of using the spatialvariation in SEM measurements to evaluate and treatment of deep andearly-stage pressure-induced injuries or ulcers.

This description is not intended to be a detailed catalog of all thedifferent ways in which the disclosure may be implemented, or all thefeatures that may be added to the instant disclosure. For example,features illustrated with respect to one aspect may be incorporated intoother aspects, and features illustrated with respect to a particularaspect may be deleted from that aspect. Thus, the disclosurecontemplates that in some aspects of the disclosure, any feature orcombination of features set forth herein can be excluded or omitted. Inaddition, numerous variations and additions to the various aspectssuggested herein will be apparent to those skilled in the art in lightof the instant disclosure, which do not depart from the instantdisclosure. In other instances, well-known structures, interfaces andprocesses have not been shown in detail in order not to unnecessarilyobscure the invention. It is intended that no part of this specificationbe construed to effect a disavowal of any part of the full scope of theinvention. Hence, the following descriptions are intended to illustratesome particular aspects of the disclosure, and not to exhaustivelyspecify all permutations, combinations, and variations thereof.

Unless otherwise defined, all technical and scientific term used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which this disclosure belongs. The terminology used in thedescription of the disclosure herein is for the purpose of describingparticular aspects or aspects only and is not intended to be limiting ofthe disclosure.

All publications, patent applications, patents and other referencescited herein are incorporated by reference in their entireties for theteachings relevant to the sentence and/or paragraph in which thereference is presented. References to techniques employed herein areintended to refer to the techniques as commonly understood in the art,including variations on those techniques or substitutions of equivalenttechniques that would be apparent to one of skill in the art.

Unless the context indicates otherwise, it is specifically intended thatthe various features of the disclosure described herein can be used inany combination. Moreover, the present disclosure also contemplates thatin some aspects of the disclosure, any feature or combination offeatures set forth herein can be excluded or omitted.

The methods disclosed herein include and comprise one or more steps oractions for achieving the described method. The method steps and/oractions may be interchanged with one another without departing from thescope of the present invention. In other words, unless a specific orderof steps or actions is required for proper operation of the aspect, theorder and/or use of specific steps and/or actions may be modifiedwithout departing from the scope of the present invention.

As used in the description of the disclosure and the appended claims,the singular forms “a,” “an” and “the” are intended to include theplural forms as well, unless the context clearly indicates otherwise.

As used herein, “and/or” refers to and encompasses any and all possiblecombinations of one or more of the associated listed items, as well asthe lack of combinations when interpreted in the alternative (“or”).

The terms “about” and “approximately” as used herein when referring to ameasurable value such as a length, a frequency, or a SEM value and thelike, is meant to encompass variations of ±20%, ±10%, ±5%, ±1%, ±0.5%,or even ±0.1% of the specified amount.

As used herein, phrases such as “between X and Y” and “between about Xand Y” should be interpreted to include X and Y. As used herein, phrasessuch as “between about X and Y” mean “between about X and about Y” andphrases such as “from about X to Y” mean “from about X to about Y.”

As used herein, the term “exemplary” is used to mean serving as anexample, instance, or illustration. Any aspect or aspect described as“exemplary” is not necessarily to be construed as preferred oradvantageous over other aspects or aspects, nor is it meant to precludeequivalent structures and techniques known to those of ordinary skill inthe art. Rather, use of the word exemplary is intended to presentconcepts in a concrete fashion, and the disclosed subject matter is notlimited by such examples.

As used herein, the term “sub-epidermal moisture” or “SEM” refers to theamount of moisture in skin tissue under the epidermis. SEM may includeintracellular and extracellular fluid. Without being bound by theory,when skin tissue is damaged, inflammation at the site of injury cancause blood vessels to dilate and increase blood flow into the skintissue. There can also be an increase in blood vessel permeability,allowing fluid, proteins, and white blood cells to migrate from thecirculation to the site of skin tissue damage. The flood of fluids,cells, and other substances to the injured site produces swelling andredness, and increases the amount of SEM in the damaged skin tissue.Processes like apoptosis and necrosis may also increase the amount offluid in the damaged region.

As used herein, “tissue biocapacitance” refers to a biophysical markerfor detecting tissue damage based on the increased level of fluids thatbuild up in the interstitial space. Without being bound by theory, thegreater the fluid content in a tissue, the higher the biocapacitancevalue. In some aspects, the methods described herein comprise a step ofmeasuring the biocapacitance in a tissue. In some aspects, the methodsdescribed herein comprise a step of measuring the biocapacitance of theskin. In some aspects, the biocapacitance measured with the methodsdescribed herein vary linearly with the SEM in the tissue. In someaspects, the biocapacitance measured with the methods described hereinvary non-linearly with the SEM in the tissue.

As used herein, “assessment of tissue health” refers to the quantitativeor qualitative measurement of the condition of a tissue. In someaspects, assessment of tissue health is performed by a visualassessment. In some aspects, assessment of tissue health is performed byskin tissue assessment. In some aspects, assessment of tissue health isperformed using electromagnetic energy. In some aspects, assessment oftissue health is performed by measuring one or more SEM values. In someaspects, assessment of tissue health is a risk analysis. In someaspects, assessment of tissue health is an analysis of the risk ofdeveloping a pressure sore or pressure ulcer. In some aspects, tissuehealth is measured by the Braden Scale. In some aspects, tissue healthis measured by the Waterlow scale. In some aspects, assessment of tissuehealth is performed by at least one of a visual assessment, skin tissueassessment, Braden scale, Waterlow scale, and measurement of SEM values.

As used herein a “patient” may be a human or animal subject.

As used herein, “extracellular fluid” or “ECF” refers to bodily fluidcontained outside of cells, including plasma, interstitial fluid, andtranscellular fluid.

As used herein, “healthy” may describe skin tissue that does not exhibitsymptoms of damage to cellular walls or blood vessels. Without beingbound by theory, the presence of an increased amount of ECF may be anindication of such skin tissue damage.

As used herein, “damaged tissue” refers to tissue that is not healthy.

As used herein, an “erythema” refers to an area of superficial skinreddening. In some aspects, damaged tissue comprises an area oferythema.

As used herein, “region” or “target region” refers to an anatomicalregion on a subject. In some aspects, a region or target region isassociated with an anatomical feature on a patient's body.

As used herein, “area,” “tissue assessment area,” or “assessment area”refers a subregion within an anatomical region. In some aspects, atissue assessment area refers to a subregion outside and away from thedamaged tissue. In some aspects, a tissue assessment area refers to asubregion at and around the damaged tissue. In some aspects, a tissueassessment area is an erythema. In some aspects, the boundary betweendifferent tissue assessment areas is delineated by an edge of anerythema.

As used herein, “location” or “measurement location” refers to aposition where an SEM measurement is collected on a subject.

As used herein, “average” refers to taking the arithmetic mean of a setof numeric values. In an aspect, the numeric values can be SEMmeasurements.

As used herein, “cut-off”, “cut-off value”, “threshold”, or “cut-offthreshold” refers to a numeric value to which measured values orcalculated values can be compared against for clinical utility.

As used herein, “spatially distinct locations” or “spatially distinctpoints” refers to two or more locations on a surface, for example, on atarget region or assessment area, that do not overlap. In some aspects,two or more locations are spatially distinct if the areas of the two ormore areas do not overlap. In some aspects, two or more locations arespatially distinct if the centers of the two or more areas do notoverlap.

As used herein, “measurement time interval” refers to a period of timebetween two sets of SEM measurements. In some aspects, a measurementtime interval is predetermined. In some aspects, a measurement timeinterval is a predetermined number of minutes. In some aspects, ameasurement time interval is a predetermined number of hours. In someaspects, a measurement time interval is a predetermined number of days.In some aspects, a measurement time interval is a predetermined numberof weeks. In some aspects, a measurement time interval is apredetermined number of months.

The present disclosure provides a system for assessing tissue health atand around a target region. In an aspect, the system comprises a devicecapable of making SEM measurements, including but not limited to thatdescribed in U.S. Pat. No. 9,398,879B2. In an aspect, the systemcomprises a device capable of making SEM measurements including but notlimited to that described in U.S. Pat. No. 10,182,740B2. Both U.S. Pat.Nos. 9,398,879B2 and 10,182,740B2 are incorporated herein by referencein their entireties. In an aspect, the system comprises a device capableof making SEM measurements, including but not limited to the SEM ScannerModel 200 (Bruin Biometrics, LLC, Los Angeles, Calif.). In an aspect,the system comprises a device capable of making biocapacitancemeasurements. In an aspect, the system is configured to perform themethods described herein. In an aspect, the system comprises aprocessor. In an aspect, the system comprises a non-transitorycomputer-readable medium electronically coupled to the processor, andcomprising instructions stored thereon that, when executed on theprocessor, perform the steps of the methods described herein.

In an aspect, the system comprises a device capable of making SEMmeasurements or biocapacitance measurements, the device comprising acoverlay. In an aspect, the coverlay may be a double-sided, copper-cladlaminate and an all-polyimide composite of a polyimide film bonded tocopper foil. In an aspect, the coverlay may comprise Pyralux 5 milFRO150. Without being limited by theory, the use of this coverlay mayavoid parasitic charges naturally present on the skin surface frominterfering with the accuracy and precision of SEM measurements.

The present disclosure provides methods for assessing tissue health atand around a target region. In an aspect, a target region comprises oneor more assessment areas. In an aspect, a target region compriseshealthy tissue. In an aspect, a target region comprises damaged tissue.In an aspect, a target region comprises tissue suspected to be damaged.

One or more target regions on a body may be associated with ananatomical feature. In an aspect, anatomical features include, but arenot limited to, the heel, lower back, sacrum, tailbone, hip, shoulderblade, ankle, elbow, ear, and the back of the head. In an aspect, atarget region corresponds to an anatomical location or anatomical site(e.g., sacrum, heel, scapula, elbow, thoracic spine, trochanter,ischium, ear, or other fleshy tissue). In an aspect, a target regioncorresponds to a bony prominence.

In some aspects, a target region is the cranial region. In some aspects,a target region is the facial region. In some aspects, a target regionis the frontal region. In some aspects, a target region is the orbitalor ocular region. In some aspects, a target region is the buccal region.In some aspects, a target region is the auricle or otic region. In someaspects, a target region is the nasal region. In some aspects, a targetregion is the oral region. In some aspects, a target region is themental region. In some aspects, a target region is the cervical region.In some aspects, a target region is the thoracic region. In someaspects, a target region is the mammary region. In some aspects, atarget region is the sternal region. In some aspects, a target region isthe abdominal region. In some aspects, a target region is the umbilicalregion. In some aspects, a target region is the coxal region (hipregion). In some aspects, a target region is the pubic region. In someaspects, a target region is the inguinal or groin region. In someaspects, a target region is the pubic region. In some aspects, a targetregion is the femoral region. In some aspects, a target region is thepatellar region. In some aspects, a target region is the crural region.In some aspects, a target region is the fibular region. In some aspects,a target region is the tarsal region. In some aspects, a target regionis the pedal region. In some aspects, a target region is thedigital/phalangeal region. In some aspects, a target region is thehallux. In some aspects, a target region is the axillary region. In someaspects, a target region is the brachial region. In some aspects, atarget region is the antecubital region. In some aspects, a targetregion is the antebrachial region. In some aspects, a target region isthe carpal region. In some aspects, a target region is the palmarregion. In some aspects, a target region is the digital/phalangealregion. In some aspects, a target region is the pollex. In some aspects,a target region is the cervical region. In some aspects, a target regionis the scapular region. In some aspects, a target region is the dorsalregion. In some aspects, a target region is the lumbar region. In someaspects, a target region is the sacral region. In some aspects, a targetregion is the cervical region. In some aspects, a target region is theacromial region. In some aspects, a target region is the brachialregion. In some aspects, a target region is the olecranal region. Insome aspects, a target region is the antebrachial region. In someaspects, a target region is the manual or manus region. In some aspects,a target region is the gluteal region. In some aspects, a target regionis the femoral region. In some aspects, a target region is the poplitealregion. In some aspects, a target region is the sural region. In someaspects, a target region is the calcaneal region. In some aspects, atarget region is the plantar region.

In an aspect, a tissue assessment area comprises an area or a volume inskin tissue where measurements of skin condition are made. In an aspect,an assessment area on a skin comprises an area on the surface of theskin. In an aspect, an assessment area on skin comprises an area on thesurface of the skin and the volume of underlying skin tissue. In anaspect, an assessment area is an area on the skin centered over a PI/PU.In an aspect, an assessment area is an area on the skin centered overdamaged tissue. In an aspect, an assessment area is an area on the skincentered over tissue suspected of having tissue damage. In an aspect, anassessment area is an area on the skin centered over tissue suspected offorming a PI/PU. In an aspect, an assessment area is an area on the skincentered over tissue at risk of forming a PI/PU. In an aspect, anassessment area is an area on the skin centered over skin withsuperficial reddening (erythema). In an aspect, an assessment area iscircular. In an aspect, an assessment area is a ring. In an aspect, anassessment area is a rectangle. In an aspect, an assessment area is aring centered over a pressure ulcer, with a radius or about 1 cm, about2 cm, about 3 cm, about 4 cm, about 5 cm, about 6 cm, about 7 cm, about8 cm, about 9 cm, or about 10 cm. In an aspect, an assessment area is aring centered over damaged tissue, with a radius or about 1 cm, about 2cm, about 3 cm, about 4 cm, about 5 cm, about 6 cm, about 7 cm, about 8cm, about 9 cm, or about 10 cm. In an aspect, an assessment area is aring centered over tissue suspected of having tissue damage, with aradius or about 1 cm, about 2 cm, about 3 cm, about 4 cm, about 5 cm,about 6 cm, about 7 cm, about 8 cm, about 9 cm, or about 10 cm. In anaspect, an assessment area is a ring centered over an erythema, with aradius or about 1 cm, about 2 cm, about 3 cm, about 4 cm, about 5 cm,about 6 cm, about 7 cm, about 8 cm, about 9 cm, or about 10 cm. In someaspects, a tissue measurement area may be the area of an erythema.

In an aspect, an edge of an erythema may be determined by visualinspection and standard skin and tissue assessment. In an aspect, anedge of an erythema may be determined by assessing the spatial variationin SEM measurements taken in a region. In an aspect, an edge of anerythema may be identified by a maximum value out of a set of SEMmeasurements.

An assessment area may comprise one or more measurement locations. Oneor more SEM measurements may be obtained at each measurement location.In an aspect, an assessment area comprises at least one, at least two,at least three, at least four, at least five, at least six, at leastseven, at least eight, at least nine, at least ten, at least 11, atleast 12, at least 13, at least 14, at least 15, at least 16, at least17, at least 18, at least 19, or at least 20 measurement locations. Insome aspects, a tissue assessment area comprises one, two, three, four,five, six, seven, eight, nine, ten, 11, 12, 13, 14, 15, 16, 17, 18, 19,or 20 measurement locations. In some aspects, a measurement location hasan area that is the area in contact with an SEM measurement device. Insome aspects, a measurement location is a point in the center of an areain contact with an SEM measurement device. In an aspect, a measurementlocation is spatially distinct from another measurement location.

In an aspect, measurement locations are in a spatially-specific patternwithin the assessment area. In an aspect, measurement locations arerandomly dispersed within the assessment area. In an aspect, the spatialpattern of measurement locations is readings is made in a pattern with atarget region in the center. In an aspect, measurements are made in oneor more circular patterns of increasing or decreasing size, cross-shapedpatterns, T-shaped patterns, a set of specific locations, or randomlyacross a region. In an aspect, measurements may be taken at locations onone or more concentric circles centered on an anatomical region.

FIG. 1A illustrates an SEM measurement strategy in the prior art showing17 spatially distinct measurement locations in one assessment area.

FIG. 1B illustrates another SEM measurement strategy in the prior artshowing 9 spatially distinct assessment locations in one assessmentarea.

FIG. 2A illustrates an exemplary SEM assessment map for an exemplaryalgorithm (“Algorithm A”) of this disclosure. In an aspect, the SEMmeasurement strategy comprises more than one assessment areas. In anaspect, a first assessment area is a circle with a first outer radius,e.g., as depicted by the dotted line in FIG. 2A. In an aspect, thecenter of a first assessment area ‘C’ comprises an area of damagedtissue, as depicted by the shaded oval in FIG. 2A. In an aspect, thecenter of a first assessment area ‘C’ is an area of damaged tissue. Inan aspect, the center of a first assessment area ‘C’ is an area oftissue with suspected damage. In an aspect, the center of a firstassessment area ‘C’ is centered over damaged tissue. In an aspect, thecenter of a first assessment area ‘C’ is an anatomical region, e.g., aheel, a sacrum. In an aspect, a second assessment area is an annuluswith a second inner radius and a third outer radius centered on ananatomical region. In an aspect, a second assessment area is an annuluswith a second inner radius and a third outer radius, centered around thefirst assessment area. In an aspect, a second assessment area is anannulus with a second inner radius and a third outer radius centeredaround an area of damaged tissue. In an aspect, a second assessment areais an annulus with a second inner radius and a third outer radiuscentered over damaged tissue. In an aspect, the second inner radius ofthe second assessment area, e.g., an annulus, is greater than the firstouter radius of the first assessment area, e.g., a circle. In an aspect,the second inner radius of the second assessment area, e.g., an annulus,is equal to the first outer radius of the first assessment area, e.g., acircle. In an aspect, the first assessment area and the secondassessment area do not overlap. In an aspect, a boundary between a firstand a second assessment areas is delineated by an edge of an erythema.In an aspect, a boundary between a first and a second assessment areasis a circle that encompasses a region of damaged tissue within thecircle. In an aspect, a boundary between a first and a second assessmentareas is a circle that encompasses a region suspected to contain damagedtissue within the circle.

In an aspect, SEM measurements are obtained at locations along two linesthat divide a circular assessment area into four quadrants, e.g., afirst line at measurement locations 16, 12, 8, 4, 2, 6, 10, and 14, anda second line at measurement locations 15, 11, 7, 3, 1, 5, 9, and 13, asdepicted in FIG. 2A. In an aspect, SEM measurements are obtained atlocations in concentric rings within a circular assessment area, e.g.,measurement locations 1, 2, 3, and 4, followed by measurement locations5, 6, 7, and 8, as depicted in FIG. 2A. In an aspect, SEM measurementsare obtained at locations along two lines that divide an annulusassessment area into four quadrants, e.g., a first line at measurementlocations 16, 12, 8, 4, 2, 6, 10, and 14, and a second line atmeasurement locations 15, 11, 7, 3, 1, 5, 9, and 13, as depicted in FIG.2A. In an aspect, SEM measurements are obtained at locations inconcentric rings within an annulus assessment area, e.g., measurementlocations 9, 10, 11, and 12, followed by measurement locations 13, 14,15, and 16, as depicted in FIG. 2A.

In an aspect, the number of measurements taken within a first assessmentarea may be fewer than the number of measurements taken within a secondassessment area. In an aspect, the number of measurements taken within afirst assessment area may exceed the number of measurements taken withina second assessment area. In an aspect, the number of measurements takenwithin a first assessment area may equal to the number of measurementstaken within a second assessment area. In an aspect, an average SEMvalue within a single assessment area is obtained from two, three, four,five, six, seven, eight, nine, ten, or more than ten SEM values measuredin an assessment area.

In an aspect, a first plurality of SEM values are measured in the firstassessment area, e.g., a circle with a first outer radius, at spatiallydistinct locations. In an aspect, a first plurality of SEM values aremeasured in the first assessment area, e.g., locations C, 1, 2, 3, 4, 5,6, 7, and 8, as depicted in FIG. 2A. In an aspect, a first average SEMvalue is calculated as the arithmetic mean of the first plurality of SEMvalues. In an aspect, a second plurality of SEM values are measured inthe second assessment area, e.g., an annulus with a second inner radiusand a third outer radius, at spatially distinct locations. In an aspect,a second plurality of SEM values are measured in the second assessmentarea, e.g., locations 9, 10, 11, 12, 13, 14, 15, and 16, as shown inFIG. 2A. In an aspect, a second average SEM value is calculated as thearithmetic mean of the second plurality of SEM values. In an aspect, afirst plurality of SEM values are measured in the first assessment area,e.g., a circle with a first outer radius, at spatially distinctlocations, and a second plurality of SEM values are measured in thesecond assessment area, e.g., an annulus with a second inner radius anda third outer radius, at spatially distinct locations. In an aspect, afirst average SEM value is calculated as the arithmetic mean of thefirst plurality of SEM values, and a second average SEM value iscalculated as the arithmetic mean of the second plurality of SEM values.In an aspect, an SEM delta value is calculated as the difference betweenthe first average SEM value and the second average SEM value. In anaspect, an SEM delta value is calculated as the difference between anaverage of the SEM measurements collected in the first assessment area,e.g., a circle, and an average of the SEM measurements collected in thesecond assessment area, e.g., an annulus.

In an aspect, the first plurality of SEM values are measured in thefirst assessment area, e.g., a circle with a first outer radius, atspatially distinct locations. In an aspect, the first plurality of SEMvalues are taken on a straight line across the first assessment area. Inan aspect, the first plurality of SEM values are taken on a curved linewithin the first assessment area. In an aspect, the first plurality ofSEM values are taken at locations on a specific pattern within the firstassessment area. In an aspect, the measurement locations of the firstplurality of SEM values are measured along 1, 2, 3, 4, 5, 6, 7, 8, 9, or10 concentric circles within the first assessment area (circle). In anaspect, the measurement locations of the first plurality of SEM valuesare spatially separated from each other at a specified distance. In anaspect, the measurement locations of the first plurality of SEM valuesare about 0.5 cm, about 1 cm, about 1.5 cm, about 2 cm, about 2.5 cm,about 3.0 cm, about 3.5 cm, about 4.0 cm, about 4.5 cm, or about 5.0 cmapart. In an aspect, the measurement locations of the first plurality ofSEM values are at least 0.5 cm, at least 1 cm, at least 1.5 cm, at least2 cm, at least 2.5 cm, at least 3.0 cm, at least 3.5 cm, at least 4.0cm, at least 4.5 cm, or at least 5.0 cm apart. In an aspect, themeasurement locations of the first plurality of SEM values are at most0.5 cm, at most 1 cm, at most 1.5 cm, at most 2 cm, at most 2.5 cm, atmost 3.0 cm, at most 3.5 cm, at most 4.0 cm, at most 4.5 cm, or at most5.0 cm apart.

In an aspect, the second plurality of SEM values are measured in thesecond assessment area, e.g., an annulus with a second inner radius anda third outer radius, at spatially distinct locations, are taken on astraight line across the second assessment area. In an aspect, thesecond plurality of SEM values are taken on a curved line within secondfirst assessment area. In an aspect, the second plurality of SEM valuesare taken at locations on a specific pattern within the secondassessment area. In an aspect, the measurement locations of the secondplurality of SEM values are measured along 1, 2, 3, 4, 5, 6, 7, 8, 9, or10 concentric circles within the second assessment area (annulus). In anaspect, the measurement locations of the second plurality of SEM valuesare spatially separated from each other at a specified distance. In anaspect, the measurement locations of the second plurality of SEM valuesare about 0.5 cm, about 1 cm, about 1.5 cm, about 2 cm, about 2.5 cm,about 3.0 cm, about 3.5 cm, about 4.0 cm, about 4.5 cm, or about 5.0 cmapart. In an aspect, the measurement locations of the second pluralityof SEM values are at least 0.5 cm, at least 1 cm, at least 1.5 cm, atleast 2 cm, at least 2.5 cm, at least 3.0 cm, at least 3.5 cm, at least4.0 cm, at least 4.5 cm, or at least 5.0 cm apart. In an aspect, themeasurement locations of the second plurality of SEM values are at most0.5 cm, at most 1 cm, at most 1.5 cm, at most 2 cm, at most 2.5 cm, atmost 3.0 cm, at most 3.5 cm, at most 4.0 cm, at most 4.5 cm, or at most5.0 cm apart.

In an aspect, a target region is flagged as containing damaged tissuewhen the SEM delta value calculated for the target region is equal to orgreater than a predetermined threshold. In an aspect, a predeterminedthreshold is about 0.6, about 0.65, about 0.7, about 0.75, about 0.8,about 0.85, about 0.9, about 0.95, or about 1.0. In an aspect, apredetermined threshold is at least 0.6, at least 0.65, at least 0.7, atleast 0.75, at least 0.8, at least 0.85, at least 0.9, at least 0.95, orat least 1.0. In an aspect, each target region of a plurality of targetregions has a different threshold. In an aspect, all target regions onthe same patient has the same threshold. In an aspect, two or moretarget regions have the same threshold. It will be understood that thepredetermined threshold is not limited by design, but rather, one ofordinary skill in the art would be capable of choosing a predeterminedvalue based on a given SEM delta value, and based on the specificanatomical regions where the measurements were performed.

In an aspect, the method according to the present disclosure does notrequire determining a maximum SEM value or a minimum SEM value from SEMvalues measured at and around an anatomical region. In an aspect, themethod according to the present disclosure does not require determininga maximum average SEM value from a plurality of average SEM values. Inan aspect, the method according to the present disclosure does notrequire determining a difference between the maximum average SEM valueand each of the average SEM values measured around an anatomical region.

In an aspect, the criteria wherein a tissue is flagged as containingdamaged tissue have both a spatial and a chronological component. In anaspect, the criteria wherein a tissue is flagged as containing damagedtissue has a spatial component when the SEM delta values are calculatedfrom a predetermined set of measurement locations within a targetregion, e.g., measurement locations as shown in FIG. 2A. In an aspect,the criteria wherein a tissue is flagged as containing damaged tissuehas a chronological component when the SEM delta values are calculatedfrom a predetermined portion of a time interval. In an aspect, a set ofSEM measurements is taken at regular intervals separated by ameasurement time interval. In an aspect, a set of SEM measurementscomprises one or more measurements taken at one or more locations in ameasurement map. In an aspect, a set of SEM measurements comprises oneor more measurements taken at each location in a measurement map, suchas but not limited to a map as illustrated in FIG. 2A. In an aspect, aset of SEM measurements comprises one or more measurements taken at asubset of locations in a measurement map. In an aspect, a set of SEMmeasurements are taken every hour, every 2 hours, every 3 hours, every 4hours, every 5 hours, every 6 hours, every 7 hours, every 8 hours, every9 hours, every 10 hours, every 11 hours, every 12 hours, every 13 hours,every 14 hours, every 15 hours, every 16 hours, every 17 hours, every 18hours, every 19 hours, every 20 hours, every 21 hours, every 22 hours,or every 23 hours. In an aspect, SEM measurements are taken every day,every 2 days, every 3 days, every 4 days, every 5 days, or every 6 days.In an aspect, a set of SEM measurements are taken every week, every 2weeks, every 3 weeks, every 4 weeks, every 5 weeks or every 6 weeks. Inan aspect, a set of SEM measurements are taken every month, every 2months, every 3 months, every 4 months, every 5 months, every 6 months,every 7 months, every 8 months, every 9 months, or every 10 months. Inan aspect, a first set of SEM measurements taken at a first timepointmay comprise a different number of SEM measurements as a second set ofSEM measurements taken at a second timepoint in the time interval. In anaspect, a first set of SEM measurements taken at a first timepoint maycomprise the same number of SEM measurements as a second set of SEMmeasurements taken at a second timepoint in the time interval. In anaspect, a first set of SEM measurements taken at a first timepointcomprises measurements from a first subset of locations in a measurementmap and a second set of SEM measurements comprises measurements from asecond subset of locations in a measurement map, wherein the first andsecond subset of locations are not the same. In an aspect, a first setof SEM measurements comprises measurements from a first subset oflocations in a measurement map and a second set of SEM measurementscomprises measurements from a second subset of locations in ameasurement map, wherein the first and second subset of locations arethe same.

In an aspect, a tissue is flagged as containing damaged tissue when theSEM delta values calculated from at least X sets of measurements out ofY consecutive sets of measurements are equal or greater than thepredetermined threshold. In an aspect, at least X measurements is atleast 1 set of measurement, at least 2 sets of measurements, at least 3sets of measurements, at least 4 sets of measurements, at least 5 setsof measurements, at least 6 sets of measurements, at least 7 sets ofmeasurements, at least 8 sets of measurements, or at least 9 sets ofmeasurements. In an aspect, Y consecutive sets of measurements is 2consecutive sets of measurements, 3 consecutive sets of measurements, 4consecutive sets of measurements, 5 consecutive sets of measurements, 6consecutive sets of measurements, 7 consecutive sets of measurements, 8consecutive sets of measurements, 9 consecutive sets of measurements, or10 consecutive sets of measurements. In an aspect, the predeterminedportion of a time interval may be defined as some portion of a differentspecific time period (weeks, month, hours etc.). In an aspect, a tissueis flagged as containing damaged tissue when the SEM delta valuescalculated from at least X days out of Y consecutive days ofmeasurements are equal or greater than the predetermined threshold. Inan aspect, at least X days is at least 1 day, at least 2 days, at least3 days, at least 4 days, at least 5 days, at least 6 days, at least 7days, at least 8 days, or at least 9 days. In an aspect, Y consecutivedays is 2 consecutive days, 3 consecutive days, 4 consecutive days, 5consecutive days, 6 consecutive days, 7 consecutive days, 8 consecutivedays, 9 consecutive days, or 10 consecutive days. In an aspect, a tissueis flagged as containing damaged tissue when the SEM delta valuescalculated from at least X hours out of Y consecutive hours ofmeasurements are equal or greater than the predetermined threshold. Inan aspect, at least X hours is at least 1 hour, at least 2 hours, atleast 3 hours, at least 4 hours, at least 5 hours, at least 6 hours, atleast 7 hours, at least 8 hours, or at least 9 hours. In an aspect, Yconsecutive hours is 2 consecutive hours, 3 consecutive hours, 4consecutive hours, 5 consecutive hours, 6 consecutive hours, 7consecutive hours, 8 consecutive hours, 9 consecutive hours, or 10consecutive hours. In an aspect, a tissue is flagged as containingdamaged tissue when the SEM delta values calculated from at least Xweeks out of Y consecutive weeks of measurements are equal or greaterthan the predetermined threshold. In an aspect, at least X weeks is atleast 1 week, at least 2 weeks, at least 3 weeks, at least 4 weeks, atleast 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, orat least 9 weeks. In an aspect, Y consecutive weeks is 2 consecutiveweeks, 3 consecutive weeks, 4 consecutive weeks, 5 consecutive weeks, 6consecutive weeks, 7 consecutive weeks, 8 consecutive weeks, 9consecutive weeks, or 10 consecutive weeks. In an aspect, a tissue isflagged as containing damaged tissue when the SEM delta valuescalculated from at least X months out of Y consecutive months ofmeasurements are equal or greater than the predetermined threshold. Inan aspect, at least X months is at least 1 month, at least 2 months, atleast 3 months, at least 4 months, at least 5 months, at least 6 months,at least 7 months, at least 8 months, or at least 9 months. In anaspect, Y consecutive months is 2 consecutive months, 3 consecutivemonths, 4 consecutive months, 5 consecutive months, 6 consecutivemonths, 7 consecutive months, 8 consecutive months, 9 consecutivemonths, or 10 consecutive months.

In an aspect, surface moisture and matter above a patient's skin surfacemay be removed prior to the measuring step. In an aspect, the measuringstep may take less than one second, less than two seconds, less thanthree seconds, less than four seconds, or less than five seconds.

In an aspect, a quality metric may be generated for any plurality ofmeasurements. In an aspect, a quality metric as used herein refers tostandards for measuring the repeatability, consistency, precision, oraccuracy of SEM measurements. Without being bound by theory, therepeatability, consistency, precision, or accuracy of SEM measurementscan be affected by many factors, including but not limited to theanatomical region of the measurement, the skill of the clinician, or theskin condition of the patient. In an aspect, the quality metric is ameasure of the repeatability of the measurements. In an aspect, thequality metric is a measure of the skill of the clinician that took themeasurement. In an aspect, the quality metric includes one or morestatistical parameters, including but not limited to an average, a mean,a standard deviation, a z-factor, or a p-value. In an aspect, a qualitymetric may be generated for any plurality of measurements made withinthe same patient. In an aspect, a quality metric may be generated forany plurality of measurements made across different patients. In anaspect, the quality metric includes a comparison of individualmeasurements to a predetermined value. In an aspect, the quality metricincludes a comparison of individual measurements to a predeterminedvalue for that particular measurement location. In an aspect, thequality metric includes a comparison of individual measurements to apredetermined value for healthy tissue. In an aspect, the quality metricincludes a comparison of individual measurements to a predeterminedvalue for damaged tissue. In an aspect, the quality metric includes acomparison of individual measurements to a predefined range. In anaspect, the quality metric includes a comparison of individualmeasurements to a predefined range determined for that particularmeasurement location. In an aspect, the quality metric includes acomparison of individual measurements to a predefined range determinedfor healthy tissue. In an aspect, the quality metric includes acomparison of individual measurements to a predefined range determinedfor damaged tissue.

In an aspect, evaluating a patient further comprises using a remotedevice, such as a computer, laptop computer, smart phone, tablet orother mobile or wearable device. In an aspect, the remote device isconfigured for intermittent monitoring. In an aspect, the remote deviceis configured for constant monitoring. In an aspect, the remote devicecommunicates wirelessly with a SEM measurement apparatus, for example aSEM scanner that comprises the capability to wirelessly communicate witha WiFi access point. In an aspect, the remote device communicateswirelessly with a SEM measurement apparatus via Bluetooth. In an aspect,the remote device is carried by the user of the SEM measurementapparatus. In an aspect, information received from the SEM measurementapparatus is stored in a database. In an aspect, information receivedfrom the SEM measurement apparatus for a patient is transferred over anetwork to another server that stores a portion of the information in anelectronic medical record (EMR) of the patient. In an aspect,information from the SEM measurement apparatus or retrieved from thedatabase or EMR is transferred to an external server and then to acomputer, for example a computer at the office of a doctor who isproviding care for the patient.

The present disclosure provides a system for assessing tissue health atand around a target region and flagging tissue as containing damagedtissue. In an aspect, the user inputs an approximate target region,e.g., heel or sacrum, into the device through a graphical user interface(GUI). In an aspect, the user inputs other information about thepatient, e.g., demographic or health information, into the devicethrough a GUI. In an aspect, the system determines the ideal measurementlocations using the methods described in the present disclosure. In anaspect, the system determines the ideal measurement locations based inpart on the target region inputted by the user. In an aspect, the systemdetermines the ideal measurement locations based in part on thedemographic information of the patient inputted by the user, e.g., ageor gender. In an aspect, the system determines the ideal measurementlocations based in part on other health information of the patientinputted by the user, e.g., age or gender. In an aspect, the systemdisplays a map of measurement locations on a GUI. In an aspect, thesystem guides a user to take measurements at specific locations based ona map of measurement locations displayed on a GUI, the map ofmeasurement locations being determined by the methods described herein.In an aspect, the system assigns each SEM measurement to a specificlocation on the map of measurement locations when it is taken. In anaspect, the system assigns each SEM measurement to a specificmeasurement time in a specific time period when measurements are taken.In an aspect, the system calculates SEM delta values based on themethods described herein. In an aspect, the system determines whether atissue is flagged as containing damaged tissue according to the methodsand criteria described herein. In an aspect, the system determineswhether a tissue is flagged as containing damaged tissue based on thespatial component of the criteria, e.g., specific measurement locations.In an aspect, the system determines whether a tissue is flagged ascontaining damaged tissue based on the chronological component of thecriteria, e.g., at least X measurements with SEM delta values equal orgreater than the predetermined threshold within Y consecutivemeasurements. In an aspect, the system flags the tissue as containingdamaged tissue by displaying a message or icon on the GUI. In an aspect,the system flags the tissue as containing damaged tissue by producing asound, e.g., a beep or alarm. In an aspect, the system determines thespecific location on the map of measurement locations that containsdamaged tissue, according to the methods described herein. In an aspect,the system displays on the GUI the specific location that containsdamaged tissue on the map of measurement locations.

In an aspect, the method further comprises performing an assessmentusing one or more objective measurements selected from the groupconsisting of: sub-epidermal moisture, bioimpedance, blood perfusion,biocapacitance, blood oxygenation, pressure measurement; capillarypressure, magnetic resonance imaging, thermal imaging, spectral imaging,ultrasound imaging, transcutaneous water loss, and detection ofinterleukin-1 alpha presence at one or more anatomical region ofinterest. In an aspect, the method further comprises performing anassess using blood perfusion, including but not limited to the methodsdescribed in U.S. Patent Publication No. US 2020/0015735 A1. In anaspect, the method further comprises performing an assessment usingultrasound, including but not limited to the methods described inInternational Patent Publication No. WO 2021/096992 A1. In an aspect,the method further comprises performing an assessment using capillarypressure measurements, including but not limited to the methodsdescribed in International Patent Publication No. WO 2021/096994 A1. Inan aspect, the method further comprises performing an assessment usingpositron emission tomography imaging, including but not limited to themethods described in International Patent Publication No. WO2021/096993. In an aspect, the method further comprises performing anassessment using thermal imaging, including but not limited to themethods described in International Patent Publication No. WO 2021/097081A1. In an aspect, the method further comprises performing an assessmentusing spectral imaging, including but not limited to the methodsdescribed in International Patent Publication No. WO 2021/097079 A1. Inan aspect, the method further comprises performing an assessment thatmeasures transepidermal water loss, including but not limited to themethods described in International Patent Publication No. WO 2021/097037A1. In an aspect, the method further comprises performing an assessmentthat detects the local interleukin-1 alpha level, including but notlimited to the methods described in International Patent Publication No.WO 2021/097083 A1. In an aspect, the method further comprises performingan assessment using magnetic resonance imaging, including but notlimited to the methods described in International Patent Publication No.WO 2021/097033 A1. In an aspect, the method further comprises performingan assessment using pressure measurements, including but not limited tothe methods described in International Patent Publication No. WO2021/096996 A1. All of U.S. Patent Publication No. US 2020/0015735 A1,and International Patent Publication Nos. WO 2021/096992 A1, WO2021/096994 A1, WO 2021/096993 A1, WO 2021/097081 A1, WO 2021/097079 A1,WO 2021/097037 A1, WO 2021/097083 A1, WO 2021/097033 A1, WO 2021/096996A1, U.S. Pat. No. 9,398,879 B2 and U.S. Pat. No. 10,182,740 B2 areincorporated herein by reference in their entireties.

Having now generally described the invention, the same will be morereadily understood through reference to the following examples that areprovided by way of illustration, and are not intended to be limiting ofthe present disclosure, unless specified.

EXAMPLES Example 1: Study Procedure for Clinical Trial Evaluating theUse of Spatial Variation in SEM Values to Determine Damaged Tissue forClinical Intervention

Subjects with Stage I or Stage II PI/PU or a suspected deep tissueinjury (sDTI) (Arm I) were recruited under protocol 003 and healthysubjects unaffected by PI/PUs (Arm II) were recruited under protocol004. For the PI/PU arm (Arm I), all enrolled subjects were residents ofnursing homes or similar care facilities with a Stage I or Stage IIPI/PU or an sDTI (suspected deep tissue injury) as confirmed by visualassessment and clinical judgment by the principal investigator andtrained, experienced facility staff. All subjects metinclusion/exclusion criteria as outlined in Table 1. Expertinvestigators and PI/PU HCPs evaluating all subjects were trained in SEMmeasurements but blinded to clinical interpretations of SEM readings.Diagnosis of patient condition was confirmed by expert physicians afterdetailed assessments and diagnosis by specialists. Principalinvestigators were responsible for final decisions made with tie-breakerdiagnosis.

TABLE 1 INCLUSION/EXCLUSION CRITERIA FOR ARM I AND ARM II Arm I:Protocol 003 Arm II: Protocol 004 Inclusion criteria Inclusioncriteria 1. Subjects ≥55 years of age 1. Subjects ≥55 years of age 2.Subject or proxy is willing and able to 2. Subject or proxy is willingand able to provide informed consent provide informed consent 3. Subjectis agreeable to having skin 3. Subject is agreeable to having skinassessments and SEM readings assessments and SEM readings performedperformed 4. Subject has a PI/PU (Stage I or II, or suspected DTI)Exclusion criteria Exclusion criteria 1. Subject has broken skin at thewound site 1. Subject has broken skin at the 2. Subjects for whom thephysical act of anatomical locations being assessed performinginspections and readings 2. Subjects with limited physical capacityrequired in this study are contra-indicated or accessibility to theanatomical 3. Subjects for whom none of the anatomical locations thatwould prohibit clinical sites where the pressure injuries are locatedevaluations and measurements to be are evaluable. performed. 4. Subjecthas pressure injuries on the face 3. Subjects or legal representativeswho are and head unable to understand the aims and 5. Subjects or legalrepresentatives who are objectives of the study. unable to understandthe aims and 4. Presence of any condition(s) that objectives of thetrial seriously compromise the subject's 6. Presence of any condition(s)which ability to complete this study. seriously compromises thesubject's ability 5. Subject has been told by a physician that tocomplete this study he/she has any one of the following: 7. Subject isComfort Measure Only (CMO) rheumatoid arthritis, gout or an statusautoimmune disorder. 8. Subject is pregnant 6. Subject is on systemic ortopical 9. Subject is incarcerated corticosteroids. Subjects usingtopical 10. Subject has participated in a clinical trial corticosteroidsare excluded only if within the last 30 days medication is placed on anyof the anatomical locations being assessed DTI—deep tissue injury;PI/PU—pressure injury or ulcer; SEM—sub-epidermal moisture

A total of 175 subjects were enrolled: 59 subjects with PI/PUs on theheel (33.7%); 63 subjects with PI/PUs on the sacrum (36%); threesubjects with PI/PUs on the thoracic spine, right trochanter and rightischium (1.7%), one each, respectively; and 50 subjects unaffected byPI/PUs (28.6%).

STAs performed at the site of PI/PU, and sacrum and heels for healthysubjects included:

-   -   Evaluation of erythema    -   PI/PU stage classification    -   Complete Braden scale or skin type question of the Waterlow        scale completed to assess an individual subject's PI/PU risk and        skin quality, respectively    -   Pain at the anatomical site of the PI/PU using a        patient-reported analogue scale (no pain to worst pain, 0-10)    -   Systemic oedema    -   Calluses    -   Scar tissue    -   Blisters

All required assessments were performed in a single study visit for botharms.

Consent, screening and enrolment occurred on the same day as/or prior tothe assessments. Demographic/physical characteristics collected at thetime of the assessment included:

-   -   Date of birth, gender, race and ethnicity    -   Height and weight

Primary and secondary admission diagnoses, admission unit, bed type anddaily functional status, as well as living situation prior to admission,were collected as indicators of functional status and considered aspotential confounders or stratifying factors. Pertinent medical historyfor each study subject, such as select comorbidities, medications andprior history of PI/PU, were collected as these factors may impact riskof PI/PU development or SEM readings. There were no protocol deviationsdue to inclusion/exclusion criteria or withdrawal criteria.

Example 2: Procedure for Taking SEM Readings

A PI/PU was defined as per NPUAP 2014 guidelines (consistent with NPIAP2019 guidelines) as a localised injury to the skin and/or underlyingtissue, usually over a bony prominence, as a result of pressure, orpressure in combination with shear. The discolored tissue consisted ofthe reddened tissue, also known as erythema of the PI/PU, or thepurple/maroon tissue of the sDTI. The periwound region was defined as aregion not exhibiting signs of any PI/PU as per expert STA. All readingswere taken spatially in the region of the bony prominence of S4 for thesacral regions and at the calcaneus for heels.

Minor modifications to the protocol were approved by the IRB beforesubject enrollment in Arm II; for example, principal investigatorsrequested not to include the ‘Southern’ readings due to modesty concernsof sacral assessments.

Example 3: Algorithms for Evaluating the Spatial Variation in SEMReadings

Mathematical models developed post hoc, based on spatial SEM readings,resulted in two algorithms: the first derived from 17 assessment points(Algorithm A) for Arm I subjects (FIG. 2B), the second from six sacraland four heel assessment points for Arm II subjects (Algorithm B).Algorithm A calculated SEM delta as a difference of the average spatialSEM readings outside of the subject's erythema (rings 2-4) and theaverage SEM readings between the center and ring 1. Algorithm Bcalculated SEM delta as a difference between the lowest and highestabsolute spatial SEM readings for a specific anatomy. Sensitivity andspecificity tables were calculated for a range of cut-off values as perthe statistical plan.

Example 4: Statistical Analysis for Evaluating the Sensitivity,Specificity, and Clinical Utility of Algorithms for Evaluating theSpatial Variation in SEM Readings

The all subject population, the safety population, the intent-to-treat(ITT) population and the per protocol population were all identical.Therefore, all tabulations and analyses were performed on and reportedfor the ITT population. Statistical analyses were performed in R CoreTeam 2013 (R Foundation, Vienna, Austria) and confirmed in JMP (SASInstitute, Cary, N.C.) or performed in SAS 9.4 (SAS Institute, Cary,N.C.). All statistical comparisons were carried out at the two-sided 5%level of significance by an independent biostatistician. Sensitivity andspecificity were calculated based on counts of true positive (TP), truenegative (TN), false positive (FP) and false negative (FN) findings asdefined by the US FDA such that:

-   -   Sensitivity=100×TP/(TP+FN)    -   Specificity=100×TN/(FP+TN)

Receiver operating characteristic (ROC) curve analysis computes andgraphically displays all combinations of sensitivity and specificity.Resulting values of ‘area under the curve’ (AUC) range from 0 to 1(0-100%), with a 45° intercept representing the line of randomness(0.5/50% sensitivity and specificity represents randomness). Diagnosticcertainty for the test increases with values above 0.5.

Example 5: Demographic Information of the Study Population

One hundred and seventy-five participants (44.6% (n=78) male and 55.4%(n=97) female) were enrolled from 16 sites in the US (53% (n=93) VB and47% (n=82) LA). All enrolled subjects completed the study. For Arm I,there were 38 procedural protocol deviations (LA: n=4; VB: n=34) relatedto missing SEM readings in the gluteal cleft—subjects' concernsregarding modesty being the reason. Additionally, there were 27procedural protocol deviations (VB) related to missing date of PI/PUdiagnosis where the nursing facility often did not record the initialdate in their records. Missing demographic data were noted for age(n=1), race (n=2) and BMI (n=3), Neither type of procedural deviationsaffected study results, There were no protocol deviations in Arm II.Missing data for race were noted in two subjects. A detailed descriptionof patient demographics is provided in Table 2.

TABLE 2 SUBJECT DEMOGRAPHICS Arm I (affected) Arm II (unaffected)p-value* Age (years) n 124 50 <0.0001 Mean (standard deviation) 82.68(10.875) 66.8 (7.282) Median (minimum, maximum) 85 (48, 99) 66 (55, 82)Gender, n (%) Female 72 (57.6%) 25 (50%) 0.402 Male 53 (42.4%) 25 (50%)Race, n (%) Non-white 39 (31.2%) 9 (18%) 0.1289 White 84 (67.2%) 39(78%) Ethnicity, n (%) Hispanic or Latino 9 (7.2%) 1 (2%) 0.2851 NotHispanic or Latino 116 (92.8%) 49 (98%) BMI (kg/m²) n 122 50 <0.0001Mean (standard deviation) 23.53 (6.429) 29.57 (6.854) Median (minimum,maximum) 22.8 (12.6, 62.4) 28.15 (19.7, 49.1) *p-values comparingaffected and unaffected subjects were generated using Fisher's Exacttest for categorical variables. p-values comparing affected andunaffected subjects were generated using an independent sample t-testwith a Satterthwaite correction in the cases where the variances werenot statistically equal for continuous variables.

Example 6: Pressure Injury/Ulcer Characteristics of Study Subjects

In Arm I, all enrolled subjects were evaluated at a single anatomical(PI/PU) location except for four subjects who presented with PI/PUs onboth heels and were assessed at both heels. Therefore, Arm I enrolled125 subjects and assessed 129 PI/PUs, 42.6% Stage I PI/PUs (n=55), 2.3%Stage II PI/PUs (n=3) and 55% sDTIs (n=71). Table 3 summarises the PI/PUstages and wound characteristics. STA results are summarised in Table 4.

TABLE 3 PRESSURE INJURY/ULCER (PI/PU) CHARACTERISTICS OF STUDY SUBJECTS(ARM I) Subjects with Subjects with heel wounds sacral wounds All (n =63 wounds (n = 66 wounds (n = 129 wounds on 59 subjects) on 66 subjects)on 125 subjects) PI/PU stage, n (%) None 0 0 0 Stage 1 13 (20.6%) 42(63.6%) 55 (42.6%) Stage 2 0 3 (4.5%) 3 (2.3%) Stage 3 or 4 0 0 0Unstageable 0 0 0 Suspected deep tissue injury 50 (79.4%) 21 (31.8%) 71(55%) Characteristics of wound edges, n (%) Indistinct, diffuse, none 25(42.4%) 48 (72.7%) 73 (58.4%) clearly visible Distinct, outline clearlyvisible, 29 (49.2%) 15 (22.7%) 44 (35.2%) attached, even with wound baseWell-defined, not attached 3 (5.1%) 2 (3%)   5 (4%) to wound baseWell-defined, not attached to base, 0 1 (1.5%) 1 (0.8%) rolled under,thickened Missing 2 (3.4%) 0 2 (1.6%) Recurring wound? n (%) No 49(83.1%) 59 (89.4%) 108 (86.4%) Yes  8 (13.6%)  7 (10.6%) 15 (12%)Missing 2 (3.4%) 0 2 (1.6%)

TABLE 4 SKIN AND TISSUE ASSESSMENT (STA) RESULTS OF STUDY SUBJECTS (ARMI) Subjects with heel Subjects with sacral wounds (n = 59) wounds (n =66) All (n = 125) Braden scale total score categories, n (%) Very highrisk: Total Score 9 6 (10.2%) 13 (19.7%) 19 (15.2%) or less High risk:Total score 10-12 14 (23.7%) 28 (42.4%) 42 (33.6%) Moderate risk: Totalscore 13-14 11 (18.6%) 10 (15.2%) 21 (16.8%) Mild risk: Total score15-18 23 (39.0%) 13 (19.7%) 36 (28.8%) No risk: Total score 19-23 5(8.5%) 2 (3.0%) 7 (5.6%) Waterlow skin type subscale, n (%) Healthy 0 00 Tissue paper 11 (18.6%) 28 (42.4%) 39 (31.2%) Dry and/or itching 3(5.1%) 5 (7.6%) 8 (6.4%) Oedematous 21 (35.6%) 0 21 (16.8%) Clammy,pyrexia 0 0 0 Discoloured, Stage 1 11 (18.6%) 30 (45.5%) 41 (32.8%)Pressure ulcer/injury, Stage 13 (22%) 3 (4.5%) 16 (12.8%) 2, 3 or 4⁺

Example 7: Spatial SEM Readings (Arm I Versus Arm II)

Data comparing spatial SEM readings at and around the heel indicated ahigher mean ‘center’ SEM reading of 1.87 (SD=0.839) for Arm I subjectscompared to 1.68 (SD=0.465) for Arm II subjects. The mean difference0.20 (95% confidence interval (CI): −0.05-0.44) did not reachstatistical significance (p=0.118). Mean readings outside of theerythema (ring 3) for the medial point were higher (mean SEM=2.1,SD=0.677) in Arm I subjects compared to similarly located points onthose in Arm II unaffected by PI/PUs (mean 1.83, SD=0.506) with a meandifference of 0.27 (95% CI: 0.05-0.49, p=0.018). Mean SEM readingdifference for the lateral point between Arm I and Arm II subjects was0.13 (95% CI: −0.06-0.32), p=0.086), approaching statisticalsignificance.

In sacral locations, the mean center SEM reading (2.18, SD=1.013) waslower in Arm I subjects (p=0.184) compared to Arm II (mean =2.36,SD=0.375). The SEM readings at the periphery of the erythema (ring 2)and outside of the erythema (ring 3) were higher in Arm I (PI/PU)subjects compared to similarly located points on those unaffected byPI/PUs, with the differences for the left and right points of ring 2 andall the points of ring 3 reaching statistical significance (p<0.05).

Example 8: SEM Readings within Arm I and Arm II

In Arm I subjects, the mean SEM readings for each subsequent ringincreased as the ring increased in distance from the center of the heelPI/PU (1.92, SD=0.89). The mean SEM reading at the center of the heelPI/PU was statistically significantly lower than the readings collectedat rings 2, 3, and 4 (p<0.01 in all cases) (Table 5).

TABLE 5 SUB-EPIDERMAL MOISTURE (SEM) READINGS BY RING FOR PRESSUREINJURY/ULCER (PI/PU) ON HEEL SEM scanner placement Estimates Centre Ring1 Ring 2 Ring 3 Ring 4 Mean (SE) 1.92 (0.10) 2.03 (0.09) 2.14 (0.09)2.20 (0.09) 2.25 (0.09) 95% CI (1.72, 2.13) (1.87, 2.21) (1.97, 2.32)(2.03, 2.37) (2.09, 2.44) Comparisons to center Difference (SE) 0.12(0.07) 0.22 (0.07) 0.28 (0.07) 0.34 (0.07) 95% CI (−0.03, 0.26)  (0.07,0.37) (0.13, 0.42) (0.19, 0.49) Two-sided p-value 0.121 0.003 <0.001<0.001 CI—confidence interval; SE—standard error

Similarly, the mean SEM reading at the center of the wounds was 2.18(SD=1.01) and mean readings increased as the ring increased in distancefrom the center of the PI/PU (p<0.001 in all cases) (Table 6).

TABLE 6 SUB-EPIDERMAL MOISTURE (SEM) READINGS BY RING FOR PRESSUREINJURY/ULCER (PI/PU) ON SACRUM SEM Scanner Placement Estimates CentreRing 1 Ring 2 Ring 3 Ring 4 Mean (SE) 2.18 (0.09) 2.36 (0.06) 2.58(0.06) 2.79 (0.06) 2.85 (0.06) 95% CI (2.01, 2.35) (2.23, 2.47) (2.47,2.71) (2.67, 2.90) (2.73, 2.97) Comparisons to center Difference (SE)0.17 (0.08) 0.41 (0.08) 0.61 (0.08) 0.67 (0.08) 95% CI (0.02, 0.33)(0.25, 0.57) (0.45, 0.76) (0.51, 0.82) Two-sided p-value 0.029 <0.001<0.001 <0.001 CI—confidence interval; SE—standard error

In Arm II subjects SEM readings at and around the bony prominence of thesacrum were not significantly different (Kruskal—Wallis chi-square=8.49,p=0.0753). However, readings at and around the bony prominence of theheel were significantly different (Kruskal—Wallis chi-square=12.49,p=0.0019).

Example 9: Confounder Evaluation

For Arm I subjects, SEM readings taken at the center of wounds did notshow any significant associations between blanchable and non-blanchableerythema (p>0.10) or pain levels (p>0.45). SEM readings approached butdid not reach statistical significance (Student's two sample t-test) byPI/PU stages (Stage I PI/PU versus deep tissue injury (DTI)) amongsubjects with heel PI/PUs (t=1.71, p=0.093) or among subjects withsacral PI/PUs (t=−1.93, p=0.059), meaning discriminating between typesof intact skin PI/PUs using the SEM test was not definitive from thisstudy.

For Arm II, all of the subject characteristics, medical history andvisual evaluation variables were considered as potential confounders.Repeated measures analysis of variance (ANOVA) was used to evaluate thevariation due to the potential confounder (between-subject variability,or ‘model’ variability) compared to the variation due to anatomicallocation (within-subject variability, or ‘error’ remaining). Resultsfrom ANOVA showed no association between gender and the spatial SEMreadings (p=0.4435). However, the Mann—Whitney—Wilcoxon rank sum testindicated that the SEM readings taken above the bony prominence of theheel were lower in male subjects than female (F test of the nullhypothesis of no between-subject variability due to gender, F=4.16,p=0.0468). No other associations between readings at the heel and genderwere observed. Calluses on the heel were identified as a potentialconfounder for heel SEM readings (F test of the null hypothesis of nobetween-subject variability due to calluses, F=15.87, p=0.0002) as wasrace (F test of the null hypothesis of no between-subject variabilitydue to race, F=9.83, p=0.003).

Example 10: Sensitivity and Specificity Algorithms for ClinicalInterpretation of the SEM Delta Value

To determine the optimal cut-off to use for clinical interpretation ofthe SEM delta, a range of cut-offs was considered using the twoalgorithms (Table 7). With Algorithm A applied to sacral SEM values, asensitivity of 90.9% was seen at the delta ≥0.6 cut-off and aspecificity of 98% was seen at the delta ≥0.9 cut-off. In contrast, SEMreadings at the heel showed the highest sensitivity (92.1%) at delta≥0.5and the highest sensitivity (96%) was seen at the delta≥0.7 cut-off. ForAlgorithm B, ≥0.6 and ≥0.7 indicated an 87.9% sensitivity for sacral SEMwith an 88% specificity at ≥0.9. For heel locations, this model showedan 85.7% sensitivity at ≥0.5 and a specificity of 58% at ≥0.8. The SEMdelta of ≥0.6 cut-off was chosen to prioritize sensitivity overspecificity.

TABLE 7 CONFIDENCE INTERVALS ON SENSITIVITY AND SPECIFICITY RESULTS Sen-Spec- Cut- sitiv- ific- off TP TN FP FN ity 95% CI ity 95% CI AlgorithmA (sacrum) ≥0.6 60 43 7 6 90.9 84.0, −97.8 86 76.4, −95.6 ≥0.7 52 46 414 78.8 68.9, −88.7 92 84.5, −99.5 ≥0.8 50 46 4 16 75.8 65.4, −86.1 9284.5, −99.5 ≥0.9 41 49 1 25 62.1 50.4, −73.8 98  94.1, −100.0 AlgorithmB (sacrum) ≥0.6 58 35 15 8 87.9 80.0, −95.8 70 57.3, −82.7 ≥0.7 58 36 148 87.9 80.0, −95.8 72 59.6, −84.5 ≥0.8 56 41 9 10 84.8 76.2, −93.5 8271.4, −92.7 ≥0.9 52 44 6 14 78.8 68.9, −88.7 88 79.0, −97.0 Algorithm A(heels) ≥0.6 52 45 5 11 82.5 73.2, −91.9 90 81.7, −98.3 ≥0.7 44 48 2 1969.8 58.5, −81.2 96  90.6, −100.0 ≥0.8 32 50 0 31 50.8 38.5, −63.1 100100.0, −100.0 ≥0.9 26 50 0 37 41.3 29.1, −53.4 100 100.0, −100.0Algorithm B (heels) ≥0.6 48 16 34 15 76.2 65.7, −86.7 32 19.1, −44.9≥0.7 45 20 30 18 71.4 60.3, −82.6 40 26.4, −53.6 ≥0.8 39 29 21 24 61.949.9, −73.9 58 44.3, −71.7 ≥0.9 36 32 18 27 57.1 44.9 −69.4 64 50.7−77.3 CI—confidence interval; FN—false negative; FP—false positive;TN—true negative; TP—true positive

At sacral locations, Algorithm A resulted in a sensitivity of 90.9% (95%CI: 84.0-97.8) and specificity of 86% (95% CI: 76.4-95.6) for an SEMdelta≥0.6 cut-off. Algorithm B resulted in 87.9% sensitivity (95% CI:80.0-95.8) and 70% specificity (95% CI: 57.3-82.7) at the delta≥0.6cut-off.

For the heels, Algorithm A resulted in 82.5% sensitivity (95% CI:73.2-91.9) and 90% specificity (95% CI: 81.7-98.3) at the delta≥0.6cut-off. Algorithm B for heels at delta≥0.6 resulted in a sensitivity of76.2% (95% CI: 65.7-86.7) and a specificity of 32% (95% CI: 19.1-44.9).Aggregate (sacrum and heel) sensitivity and specificity analysis atdelta≥0.6 using Algorithm A resulted in a sensitivity of 86.8%(n=112/129) and specificity of 88% (n=88/100). Sensitivity of 82.2%(n=106/129) and specificity of 51% (n=51/100) were noted using AlgorithmB with delta≥0.6 (Table 8). ROC curve analysis conducted post hoccomputed an area under the curve (AUC) of 0.9181 (95% CI: 0.8817,0.9545, p<0.001) for Algorithm A and an AUC of 0.7809 (95% CI: 0.7221,0.8397, p<0.0001) for Algorithm B.

TABLE 8 AGGREGATE SENSITIVITY AND SPECIFICITY RESULTS Algorithm AAlgorithm B Arm I Arm II Arm I Arm II Test True positives Falsepositives Test True positives False positives positive 112 12 positive106 49 86.80% 12.00% 82.20% 49.00% Test False negatives True negativesTest False negatives True negatives negative 17 88 negative 23 51 13.20%88.00% 17.80% 51.00% n* = 129 n** = 100 n* = 129 n** = 100 *n = 129wounds on 125 subjects-Arm I **n = 100 control sites on 50 subjects-ArmII

A variety of further modifications and improvements in and to thecompositions and methods of the present disclosure will be apparent tothose skilled in the art based. The following non-limiting embodimentsare envisioned:

Embodiment 1. A method for assessing tissue health at and around atarget region, comprising the steps of:

-   -   obtaining a first plurality of SEM measurements at a first        plurality of locations within a first tissue assessment area,    -   obtaining a second plurality of SEM measurements at a second        plurality of locations within a second tissue assessment area,    -   calculating a first average of the first plurality of SEM        measurements,    -   calculating a second average of the second plurality of SEM        measurements,    -   calculating a difference between the second average and the        first average,    -   flagging that the tissue is damaged if the difference is greater        than or equal to a cut-off threshold.

Embodiment 2. The method of embodiment 1, wherein the cut-off thresholdis a predetermined number.

Embodiment 3. The method of embodiment 2, wherein the cut-off thresholdis a number ranging from about 0.6 to about 0.9.

Embodiment 4. The method of embodiment 2, wherein the cut-off thresholdis about 0.6.

Embodiment 5. The method of embodiment 2, wherein the cut-off thresholdis about 0.7.

Embodiment 6. The method of embodiment 2, wherein the cut-off thresholdis about 0.8.

Embodiment 7. The method of embodiment 2, wherein the cut-off thresholdis about 0.9.

Embodiment 8. The method of embodiment 1, wherein the first tissueassessment area is a circle centered on the target region and having afirst radial distance.

Embodiment 9. The method of embodiment 8, wherein the second tissueassessment area is an annulus centered on the target region and having asecond inner radial distance and a third outer radial distance from thetarget region.

Embodiment 10. The method of embodiment 9, wherein the second innerradial distance is greater than or equal to the first radial distance.

Embodiment 11. The method of embodiment 9, wherein the third outerradial distance is greater than the second inner radial distance.

Embodiment 12. The method of embodiment 8, wherein the first pluralityof locations comprises a location in the center of the circle.

Embodiment 13. The method of embodiment 8, wherein the first pluralityof locations comprises spatially distinct points within the circle.

Embodiment 14. The method of embodiment 8, wherein the first pluralityof locations comprises spatially distinct points along one or moreconcentric rings within the circle, and wherein the one or moreconcentric rings are centered on the target region.

Embodiment 15. The method of embodiment 8, wherein the first pluralityof locations comprises spatially distinct points along two linesdividing the circle into four quadrants.

Embodiment 16. The method of embodiment 9, wherein the second pluralityof locations comprises spatially distinct points within the annulus.

Embodiment 17. The method of embodiment 9, wherein the second pluralityof locations comprises spatially distinct points along one or moreconcentric rings within the annulus, and wherein the one or moreconcentric rings are centered on the target region.

Embodiment 18. The method of embodiment 9, wherein the second pluralityof locations comprises spatially distinct points along two linesdividing the annulus into four quadrants.

Embodiment 19. The method of embodiment 1, wherein the first pluralityof SEM measurements consists of 1 to 9 measurements.

Embodiment 20. The method of embodiment 1, wherein the second pluralityof SEM measurements consists of 3 to 8 measurements.

Embodiment 21. The method of embodiment 1, wherein the target region isa bony prominence selected from the group consisting of a sacrum, aheel, a sternum, a scapula, an elbow, a thoracic spine, a trochanter, anischium, and an ear.

Embodiment 22. The method of embodiment 1, wherein the target region isa fleshy tissue.

Embodiment 23. The method of embodiment 1, wherein the target region iswithin an erythema.

Embodiment 24. The method of embodiment 1, wherein the target region iswithin a healthy tissue.

Embodiment 25. A system for assessing tissue health at and around atarget region, comprising:

-   -   (a) a Sub-Epidermal Moisture (SEM) scanner configured to make        SEM measurements;    -   (b) a processor electronically coupled to the SEM scanner and        configured to receive the SEM measurements; and    -   (c) a non-transitory computer readable media that is        electronically coupled to the processor and comprises        instructions stored thereon that, when executed on the        processor, performs the steps of:        -   (i) receiving a first plurality of SEM measurements at a            first plurality of locations within a first tissue            assessment area,        -   (ii) receiving a second plurality of SEM measurements at a            second plurality of locations within a second tissue            assessment area,        -   (iii) calculating a first average of the first plurality of            SEM measurements,        -   (iv) calculating a second average of the second plurality of            SEM measurements,        -   (v) calculating a difference between the second average and            the first average,        -   (vi) indicating that the tissue is damaged if the difference            is greater than or equal to a cut-off threshold.

Embodiment 26. The system of embodiment 25, wherein the cut-offthreshold is a predetermined number.

Embodiment 27. The system of embodiment 26, wherein the cut-offthreshold is a number ranging from about 0.6 to about 0.9.

Embodiment 28. The system of embodiment 26, wherein the cut-offthreshold is about 0.6.

Embodiment 29. The system of embodiment 26, wherein the cut-offthreshold is about 0.7.

Embodiment 30. The system of embodiment 26, wherein the cut-offthreshold is about 0.8.

Embodiment 31. The system of embodiment 26, wherein the cut-offthreshold is about 0.9.

Embodiment 32. The system of embodiment 25, wherein the first tissueassessment area is a circle centered on the target region and having afirst radial distance.

Embodiment 33. The system of embodiment 32, wherein the second tissueassessment area is an annulus centered on the target region and having asecond inner radial distance and a third outer radial distance from thetarget region.

Embodiment 34. The system of embodiment 33, wherein the second innerradial distance is greater than or equal to the first radial distance.

Embodiment 35. The system of embodiment 33, wherein the third outerradial distance is greater than the second inner radial distance.

Embodiment 36. The system of embodiment 32, wherein the first pluralityof locations comprises a location in the center of the circle.

Embodiment 37. The system of embodiment 32, wherein the first pluralityof locations comprises spatially distinct points within the circle.

Embodiment 38. The system of embodiment 32, wherein the first pluralityof locations comprises spatially distinct points along one or moreconcentric rings within the circle, and wherein the one or moreconcentric rings are centered on the target region.

Embodiment 39. The system of embodiment 32, wherein the first pluralityof locations comprises spatially distinct points along two linesdividing the circle into four quadrants.

Embodiment 40. The system of embodiment 33, wherein the second pluralityof locations comprises spatially distinct points within the annulus.

Embodiment 41. The system of embodiment 33, wherein the second pluralityof locations comprises spatially distinct points along one or moreconcentric rings within the annulus, and wherein the one or moreconcentric rings are centered on the target region.

Embodiment 42. The system of embodiment 33, wherein the second pluralityof locations comprises spatially distinct points along two linesdividing the annulus into four quadrants.

Embodiment 43. The system of embodiment 25, wherein the first pluralityof SEM measurements consists of 1 to 9 measurements.

Embodiment 44. The system of embodiment 25, wherein the second pluralityof SEM measurements consists of 3 to 8 measurements.

Embodiment 45. The system of embodiment 25, wherein the target region isa bony prominence selected from the group consisting of a sacrum, aheel, a sternum, a scapula, an elbow, a thoracic spine, a trochanter, anischium, and an ear.

Embodiment 46. The system of embodiment 25, wherein the target region isa fleshy tissue.

Embodiment 47. The system of embodiment 25, wherein the target region iswithin an erythema.

Embodiment 48. The system of embodiment 25, wherein the target region iswithin a healthy tissue.

1. A method for assessing tissue health at and around a target region,comprising the steps of: obtaining a first plurality of SEM measurementsat a first plurality of locations within a first tissue assessment area,obtaining a second plurality of SEM measurements at a second pluralityof locations within a second tissue assessment area, calculating a firstaverage of the first plurality of SEM measurements, calculating a secondaverage of the second plurality of SEM measurements, calculating adifference between the second average and the first average, flaggingthat the tissue is damaged if the difference is greater than or equal toa cut-off threshold.
 2. The method of claim 1, wherein the cut-offthreshold is a predetermined number.
 3. The method of claim 2, whereinthe cut-off threshold is a number ranging from about 0.6 to about 0.9.4. The method of claim 2, wherein the cut-off threshold is about 0.6. 5.The method of claim 2, wherein the cut-off threshold is about 0.7. 6.The method of claim 2, wherein the cut-off threshold is about 0.8. 7.The method of claim 2, wherein the cut-off threshold is about 0.9. 8.The method of claim 1, wherein the first tissue assessment area is acircle centered on the target region and having a first radial distance.9. The method of claim 8, wherein the second tissue assessment area isan annulus centered on the target region and having a second innerradial distance and a third outer radial distance from the targetregion.
 10. The method of claim 9, wherein the second inner radialdistance is greater than or equal to the first radial distance.
 11. Themethod of claim 9, wherein the third outer radial distance is greaterthan the second inner radial distance.
 12. The method of claim 8,wherein the first plurality of locations comprises a location in thecenter of the circle.
 13. The method of claim 8, wherein the firstplurality of locations comprises spatially distinct points within thecircle.
 14. The method of claim 8, wherein the first plurality oflocations comprises spatially distinct points along one or moreconcentric rings within the circle, and wherein the one or moreconcentric rings are centered on the target region.
 15. The method ofclaim 8, wherein the first plurality of locations comprises spatiallydistinct points along two lines dividing the circle into four quadrants.16. The method of claim 9, wherein the second plurality of locationscomprises spatially distinct points within the annulus.
 17. The methodof claim 9, wherein the second plurality of locations comprisesspatially distinct points along one or more concentric rings within theannulus, and wherein the one or more concentric rings are centered onthe target region.
 18. The method of claim 9, wherein the secondplurality of locations comprises spatially distinct points along twolines dividing the annulus into four quadrants.
 19. The method of claim1, wherein the first plurality of SEM measurements consists of 1 to 9measurements.
 20. The method of claim 1, wherein the second plurality ofSEM measurements consists of 3 to 8 measurements.
 21. The method ofclaim 1, wherein the target region is a bony prominence selected fromthe group consisting of a sacrum, a heel, a sternum, a scapula, anelbow, a thoracic spine, a trochanter, an ischium, and an ear.
 22. Themethod of claim 1, wherein the target region is a fleshy tissue.
 23. Themethod of claim 1, wherein the target region is within an erythema. 24.The method of claim 1, wherein the target region is within a healthytissue.